P62 OBJECTIVE: Impaired cerebral vasomotor reactivity has been proposed as a measure of exhausted vascular reserve in patients with carotid artery stenosis or occlusion. We tested this hypothesis by ...measuring vasoreactivity in patients with asymptomatic or recently symptomatic severe carotid artery disease. METHODS: Fourteen patients with severe carotid artery disease (5 with occlusion, 9 with stenosis 80–99%, 8 symptomatic, 6 asymptomatic within 2 years) and 7 healthy controls had continuous bilateral monitoring of mean flow velocity (MFV) in the MCAs by transcranial Doppler (TCD). End-tidal CO2 was measured continuously with an in-line capnometer connected via snorkel mouthpiece, nasal airway occluded by noseclip. After baseline measurements, subjects held their breath for 30 seconds. A breath holding index (BHI) was calculated (% change in MFV/seconds held). After return to baseline MFV, subjects breathed a 5% CO2 gas mixture for 2 minutes. CO2 reactivity was calculated as percent rise in MFV per mmHg PCO2 once the MFV curve plateaued. ANOVA was used to calculate differences between symptomatic, asymptomatic and control groups for CO2 reactivity and BHI. RESULTS: There was a highly significant difference in vasoreactivity by CO2 inhalation in the symptomatic group (2.02±.80 %/mmHg) versus the asymptomatic group (4.45±1.9 %/mmHg) and controls (3.69±.95 %/mmHg) (F 2,18 =7.85, p=.004). A linear relationship was seen between MFV and PCO2, taking multiple MFV measurements at various PCO2 levels throughout the study period (average r 2 =.60 for patients, .77 for controls). BHI did not distinguish between the groups (p=.37). CONCLUSIONS: Measuring cerebral vasoreactivity by CO2 inhalation with continuous TCD monitoring provides an important physiological index of the clinical status of patients with carotid artery disease which may help guide treatment algorithms. The linear relationship between MCA MFV and end-tidal CO2 enables confirmation of the baseline and maximum measurements used to calculate CO2 reactivity, and provides the opportunity to investigate further the link between physiology and clinical state.
Background Matrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum ...MMP-12 concentrations and activity is not known. Objectives We sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD. Methods In 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR qPCR), diffusing capacity for carbon monoxide (D lco ), and CT assessment of emphysema (percentage of low-attenuation areas at less −950 Hounsfield units). Results Sputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers ( P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or D lco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity. Conclusions Sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema.
Preliminary validation of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) for motor skill assessment in spinal muscular atrophy type I.
A total of 27 ...subjects 3 to 260 months old (mean = 49, SD = 69) with spinal muscular atrophy-I were evaluated with the CHOP INTEND. Subjects were evaluated as part of a multicenter natural history study.
CHOP INTEND scores and age were significantly correlated (r = -0.51, P = .007; 2 survival of the motor neuron SMN 2 gene copies, n = 16, r = -0.60, 3 SMN2 gene copies, n = 9, r = -0.83). Respiratory support and CHOP INTEND scores were correlated (r = -0.74, P < .0001, n = 26). The CHOP INTEND and age regression in patients with 2 copies versus 3 copies of SMN2 approached significance (P = .0711, n = 25). Subjects who required respiratory support scored significantly lower (mean = 15.5, SD = 10.2 vs mean = 31.2, SD = 4.2, P < .0001, n = 27). Correlation with motor unit number estimation and combined motor unit activation were not significant.
The CHOP INTEND reflects measures of disease severity and supports continued exploration of the CHOP INTEND.
Biofilm Research Group, Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada
Pseudomonas aeruginosa frequently acts as an opportunistic ...pathogen of mucosal surfaces; yet, despite causing aggressive prostatitis in some men, its role as a pathogen in the prostate has not been investigated. Consequently, we developed a Ps. aeruginosa infection model in the rat prostate by instilling wild-type (WT) Ps. aeruginosa strain PAO1 into the rat prostate. It was found that Ps. aeruginosa produced acute and chronic infections in this mucosal tissue as determined by bacterial colonization, gross morphology, tissue damage and inflammatory markers. WT strain PAO1 and its isogenic mutant PAO-JP2, in which both the lasI and rhlI quorum-sensing signal systems have been silenced, were compared during both acute and chronic prostate infections. In acute infections, bacterial numbers and inflammatory markers were comparable between WT PA01 and PAO-JP2; however, considerably less tissue damage occurred in infections with PAO-JP2. Chronic infections with PAO-JP2 resulted in reduced bacterial colonization, tissue damage and inflammation as compared to WT PAO1 infections. Therefore, the quorum-sensing lasI and rhlI genes in Ps. aeruginosa affect acute prostate infections, but play a considerably more important role in maintaining chronic infections. We have thus developed a highly reproducible model for the study of Ps. aeruginosa virulence in the prostate.
Correspondence Howard Ceri ceri{at}ucalgary.ca
Abbreviations: AHL, N -acylhomoserine lactone; H&E, haematoxylin and eosin; MN, mononuclear; MPO, myeloperoxidase; p.i., post-infection; PMN, polymorphonuclear; WT, wild-type
To characterize the short-term course of spinal muscular atrophy (SMA) in a genetically and clinically well-defined cohort of patients with SMA.
A comprehensive multicenter, longitudinal, ...observational study.
The Pediatric Neuromuscular Clinical Research Network for SMA, a consortium of clinical investigators at 3 clinical sites.
Sixty-five participants with SMA types 2 and 3, aged 20 months to 45 years, were prospectively evaluated.
We collected demographic and medical history information and determined the SMN 2 copy number.
Clinical outcomes included measures of motor function (Gross Motor Function Measure and expanded Hammersmith Functional Motor Scale), pulmonary function (forced vital capacity), and muscle strength (myometry). Participants were evaluated every 2 months for the initial 6 months and every 3 months for the subsequent 6 months. We evaluated change over 12 months for all clinical outcomes and examined potential correlates of change over time including age, sex, SMA type, ambulatory status, SMN2 copy number, medication use, and baseline function.
There were no significant changes over 12 months in motor function, pulmonary function, and muscle strength measures. There was evidence of motor function gain in ambulatory patients, especially in those children younger than 5 years. Scoliosis surgery during the observation period led to a subsequent decline in motor function.
Our results confirm previous clinical reports suggesting that SMA types 2 and 3 represent chronic phenotypes that have relatively stable clinical courses. We did not detect any measurable clinical disease progression in SMA types 2 and 3 over 12 months, suggesting that clinical trials will have to be designed to measure improvement rather than stabilization of disease progression.
The consensus statement for standard of care in SMA recommends multidisciplinary medical care including physical therapy (PT) services. To date there are no reports regarding the implementation of ...these recommendations and the type of care or services received by individuals with SMA. The purpose of this study is to describe the PT services received by individuals with SMA.
Interviews were conducted with patients or their caregivers at the Pediatric Neuromuscular Clinical Research (PNCR) Network sites from October 2011 to September 2012. Questions included information about clinical status of the patient, sociodemographic profile of the patient or caregiver, and PT services received in the past year, including the setting, frequency, duration and type of PT, and therapies administered by caregivers.
Eighty-six percent of 105 participants reported receiving PT services, some in multiple settings: 62% in the neuromuscular clinic, 38% at school, 34% at home, and 13% in an outpatient clinic. Greater frequency of PT services received was associated with younger age and inability to walk, but not SMA type.
This is the first multicenter study documenting PT services received by patients with SMA. Further research is needed to better understand the impact of PT services on the natural history of SMA.
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